There is no small-diameter (< 5mm internal diameter) vascular prosthesis clinically available that is capable of emulating the biological and physical properties of the normal arterial wall. The goal of this two-year phase I project, which unites a diverse group of industrial, biomedical and academic researchers, is to develop in vitro a novel nanofibrous bioactive small-diameter prosthetic vascular graft using electrospinning technology. The resulting vascular graft would possess both biological (antithrombogenic and mitogenic) and physical properties comparable to that of native artery, thereby improving graft patency. Our hypothesis is that the next generation of prosthetic arterial grafts will have to possess multiple structural and biological properties that mimic some of those processes inherent to native arteries in order to prevent complications such as thrombosis from occurring. A small-diameter nanofibrous biocomposite vascular graft will be electrospin from polyester (Dacron) and collagen, thereby possessing properties similar those of native artery. The potent antithrombin agent recombinant hirudin (rHir) and endothelial mitogen vascular endothelial growth factor (VEGF) will be covalently bound to collagen within the construct. The elastic properties of the electrospin polymer will provide circumferential compliance, with kink-resistance prevented by a thin braided Dacron mesh within the graft wall. The specific objectives are to: 1) develop electrospinning methodology for a Dacron/collagen composite graft (ESDC), 2) incorporate novel inner-wall reinforcement for ESDC, 3) synthesize novel small-diameter ESDC graft containing inner-wall reinforcement, 4) characterize physical properties of ESDC graft, 5) immobilize rHir and VEGF to ESDC graft, 6) examine surface antithrombin properties, 7) evaluate surface mitogenic properties and 8) assess surface rHirNEGF stability under simulated arterial flow conditions. Phase II of this project will evaluate this novel ESDC-rHir- VEGF graft in a canine carotid grafting model. Development of a bioactive small-diameter vascular graft would have a significant impact on small vessel repair and replacement. These grafts could be utilized in peripheral bypass as well as for coronary artery bypass, which have some 500,000 grafts implanted annually in the United States. Potentially, the annual market value for an "off-the-shelf' synthetic coronary artery bypass graft could exceed $1.5 billion.